Project summary The effective and efficient utilization of the big data accumulated in biomedical sciences, including the genomic, imaging data collected from patients that are often integrated with their electronic health records represents a great opportunity as well as a big challenge for the biomedical data science. Because biomedical data are collected from individual patients, and thus carry identifiable information of the data donors, the projection of their privacy becomes an important concern in large-scale projects including the recently launched Precision Medicine Initiative. In the past few years, significant progresses have been made on cryptographic techniques, including the homomorphic encryption (HME) that enables a direct analysis of encrypted data without decrypting it, and the Secure Multiparty Computing (SMC) that allows two or more organizations to jointly compute a task without exposing to each other?s inputs. Here, based on these techniques, we propose to develop a suite of encryption protocols and open-source software tools that can be used by biomedical researchers in a plug-and-play manner for the statistical analysis of encrypted biomedical data. We note that our methods assume biomedical data will be protected by encryption once they are generated, and the subsequent analysis and sharing will always be performed on the encrypted form, which thus can achieve a high security standard for privacy protection.